The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/.

Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/ is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring at our center. Thirty-six AML patients harboring were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK-RAS GTPase (RAS) pathway genes, including (33%) and (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of , the target of venetoclax, in AML compared to AML, a more common AML subtype with good prognosis. The median event-free survival in patients with AML was 11.9 (95% confidence interval [CI]: 9.0-not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4-NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK-RAS pathway mutations and high expression of may indicate promising therapeutic targets in this high-risk AML subset.